Current cleaning practices in the pharmaceutical, personal care, food and cosmetic manufacturing industries involve the use of alkaline, acid and/or neutral pH detergent systems for cleaning and removal of various soil residues. Areas of cleaning include reactors, storage vessels, tanks, pipes and other stainless steel equipment, with or without Clean-in-Place (CIP) systems or manual scrubbing. Current cleaning chemistries involve different mechanisms, such as solubilization, wetting, emulsification, dispersion, chelation, and chemical or enzymatic hydrolysis, and other well known physical and chemical phenomena, in addition to reactive chemistries, for the purpose of removing unwanted soils. In general, many soils can be cleaned and removed using one of the aforementioned cleaning mechanisms, but some soils require cleaning methods involving a combination of two or more different mechanisms. Soils requiring a combination of multiple cleaning agents (mechanisms) may be classified as “difficult or hard-to-clean” soils. Types of soils in this category include, but are not limited to, various hydrophobic soils, polymers, silicone-based products, cosmetics or personal care products with complex formulations (e.g. water-proof mascara), proteins, and inorganic-based products.
Alkaline cleaners promote saponification of fatty soils, which aids cleaning efficiency and increases conductivity of the solution to aid in electrolytic processes. Highly alkaline cleaners are used, both for cleaning and sanitizing, for hard surface cleaning applications and for manufacturing equipment, including Clean-in-Place applications.
Alkaline cleaning compositions are well known in the art. By way of illustration only, U.S. Pat. No. 6,581,613 to Berkels et al. discloses a composition comprising 0.1-50% of a defined alkylpolyglucoside (D.P. 1.7 to 3 and an alkyl radical comprising 8 carbon atoms) and 50 to 99.9% of a concentrated alkali metal hydroxide solution, for use in breweries and dairies.
U.S. Pat. Nos. 6,274,541, 6,479,453 and 7,037,884 to Man disclose an alkaline cleaning composition comprising an alkyl or alkylaryl ethoxy carboxylate (0.1-20 wt. %), a strong chelating agent, such as NTA, EDTA, HEDTA, and DTPA, preferably EDTA (1-20 wt. %), and a source of alkalinity, preferably a combination of ammonia or ammonium hydroxide, monoethanolamine and sodium hydroxide (2-30 wt. %) stated to be especially effective for removing lime-soaps in greasy soils from hard quarry or ceramic tile.
H468 to Malik et al., a statutory invention record, discloses a process for cleaning a soiled hard surface by applying an alkaline cleaner comprising an alkalinity source 0.1-50 wt. % and an alkylglucoside (0.1 to 40 wt. %), which is stated to be superior to alkaline cleaning compositions comprising anionic and nonionic surfactants for hard surface cleaning. The formulation also contemplates the addition of phosphate builders and the use of water miscible solvents.
U.S. Pat. No. 6,541,442 to Johansson discloses an alkaline composition containing a high amount (up to 30 wt. %) of a nonionic alkylene oxide adduct surfactant and a hexyl glucoside as a hydrotrope, for use in cleaning hard surfaces, in a mercerization process, and to clean, desize and scour fibers and fabrics at a pH above 11. The composition also includes complexing agents, such as phosphates and NTA and EDTA.
U.S. Pat. No. 6,537,960 to Ruhr et al discloses a low-foaming surfactant blend for use in highly alkaline conditions comprising at least one C3 to C10 alkyl polyglucoside, at least one amine oxide, at least one polycarboxylated alcohol alkoxylate and at least one alcohol alkoxylate. The disclosed surfactant is stated to facilitate chlorine stability.
U.S. Pat. No. 5,767,056 to Lenoir discloses an aqueous alkaline composition comprising an alkali metal hydroxide and an addition reaction product of an alcohol having 6-18 carbon atoms, with either propylene oxide and ethylene oxide or butylene oxide and ethylene oxide, for cleaning surfaces of fruits, vegetables, containers for food, or for chemical peeling of fruit or vegetables, metal working or cotton mercerization.
Cleaning compositions with analyzable surfactants are also known in the art. For example, U.S. Pat. No. 6,232,280 to Shah et al. discloses a cleaning composition comprising, as its sole surfactant, a UV-analyzable surfactant in combination with a strong alkali.
Alkaline cleaning compositions of the prior art suffer from a number of disadvantages or drawbacks. While increased active alkali content is generally associated with improved cleaning performance, use of highly alkaline compositions has been limited due to the instability of various components included in the compositions to enhance their properties. In particular, certain oxidants, surfactants, hydrotropes, foaming agents and the like are difficult to incorporate into a highly alkaline composition, so that the final product is stable in storage for a reasonable shelf life. As a result, an optimal cleaning composition, comprising components necessary to remove “hard-to-clean” soils effectively has been difficult to achieve, much less one that also possesses antimicrobial activity. Further, dilution of concentrated, highly alkaline cleaning compositions often results in less than optimal cleaning performance.
There are other drawbacks to the use of current, commercially available alkaline cleaning products for manufacturing. Many detergent systems employ the use of chelating agents, such as tetrasodium ethylenediaminetetraacetate (EDTA) or nitrilotriacetate (NTA), which are not considered totally biodegradable. NTA has also been classified as a possible carcinogen to humans (Group 2B) by the Insecticide Restrictions Action Committee (IRAC)'s working group. Further, certain surfactants used in most alkaline cleaners are not biodegradable, and, therefore, cannot be used in certain geographic areas, such as for example Europe, due to regulatory restrictions (EU 648/2004). Thus, achieving cleaning efficacy required the use of components that are not environmentally friendly or safe.
Another major disadvantage with many prior art cleaning compositions is that it is often difficult to detect whether any cleaning solution or surfactant from the cleaning solution remains on the cleansed surface in order to validate the cleaning process. Manufacturers are often required to validate the cleaning process and assure consumers and regulatory agencies that contaminants from product residues or cleaning compositions, or both, do not adulterate or adversely affect the quality and safety of the next products made in the same production vessels. It is therefore critically important that the cleaning process effectively removes both product (soil) and cleaner residues from the equipment to avoid any cross contamination from one batch to another.
Validation of cleaning procedures is an FDA requirement for drug manufacturers. Detection of contaminants requires the use of suitable analytical methods for measuring an analyte at or below a present acceptance residue limit, including specific and nonspecific methods to determine the presence or absence of component of a cleaning solution, preferably an active compound or surfactant. Examples of specific methods that detect a unique compound in the presence of potential contaminants are, but not limited to: High Performance Liquid Chromatography (HPLC), ion chromatography, atomic absorption, Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and capillary electrophoresis. Examples of nonspecific methods are, but not limited to: total organic carbon (TOC), pH, acid/base titrations and conductivity.
It is a common practice to determine the level of residual cleaning product by a non-specific analytical method, such as Total Organic Carbon (TOC) analysis. This approach is limited, however, in that it only offers information about the water-soluble carbon content of all components in the residue and not about specific components in the cleaning product. Other non-specific methods suffer from the same disadvantages.
High Performance Liquid Chromatography (HPLC) is the method of choice for determining the level of residual pharmaceutical product on equipment. It is a highly effective and sensitive analytical technique to detect specific components not only of product residue, but also of the cleaning composition employed. Pharmaceutical companies often analyze rinse solutions (rinsate) using HPLC methods with UV detection. HPLC uses a combination of chromatography for separating the rinsate into components and UV/visible spectroscopy at a fixed wavelength for detection, depending on the component to be analyzed. HPLC is set up to detect for signals at two (or more) wavelengths—one corresponding to a known component of the pharmaceutical (or other chemical) product expected to be remaining in the equipment after processing, and one corresponding to the analyzable component of the cleaning composition. Identification of the analyzable component of the cleaning composition indicates whether the cleaning composition has been thoroughly removed from a surface or equipment, after the cleaning process.
The FDA requirements are covered under the 1963 GMP regulations (Part 133.4) and Section 211.67 in the 1978 CGMP regulations (211.67). The primary rationale for requiring clean equipment validation is to prevent adulteration of drug products. The regulations require companies to have written, standard operating procedures (SOPs) detailing the cleaning processes used for various pieces of equipment, a system for validation of the cleaning processes including predetermined limits or acceptance criteria and revalidation, and a final validation report. Cleaning validation procedures involve testing for residues in the manufacturing process, selection of residue detection methods, identification of residues, selection of sampling method, setting acceptance criteria for the residues, and methods validation and recovery studies. Although the FDA does not set acceptance specifications or methods for determining whether a cleaning process is validated, some limits that are prevalent in the industry as set forth in literature include analytical detection levels such as 10 ppm, biological activity levels, such as 1/1000 of the normal therapeutic dose, and organoleptic levels as no visible residue. It is impractical for the FDA to set specific acceptance specifications due to the wide variation in equipment and products that would need to be addressed. It is preferred in the pharmaceutical industry to use a detection method involving HPLC at concentrations of around 10 ppm or less, in addition to other available methods.
Many surfactants and other components employed in current commercially available cleaning compositions cannot be quantitatively analyzed/detected in the rinse solutions by companies who are required or desire to validate their cleaning processes. Most cleaning compositions do not contain a surfactant having an analyzable species, or chromophore, which can be detected by HPLC with UV detectors. A cleaning composition with a UV-analyzable surfactant offers dual advantages, since the same analytical procedure that is used to monitor for pharmaceutical (product) residues will be used to detect for surfactant and thus validate the cleaning process.
There are other disadvantages associated with currently available cleaning compositions used in the manufacturing industry. Some cleaning compositions include disinfectants and sanitizing components, which require separate post-cleaning treatments. Cleaning compositions containing these components are known to introduce issues of their own, including instability, foaming, residues, toxicity and incompatibility (e.g., phenolics, quaternium ammonium products, peroxides, sodium hypochlorite). It is desirable therefore to have a cleaning composition which itself has enhanced antimicrobial activity, but does not require the addition of known disinfectants or sanitizing agents or a separate sanitizing or disinfecting step to achieve that activity.
Therefore, there is a need for an effective cleaning composition(s) for hard-to-clean soils, which combines the advantages of the prior art compositions without the concomitant disadvantages associated with their use. In short, there is a need for effective cleaning composition(s) for hard-to-clean soils, which have superior cleaning performance to currently available products, are phosphate-free, biodegradable, non-toxic and non-carcinogenic, and can be easily validated through conventional techniques employed by manufacturers. There is also a need for such a composition to have hospital grade disinfectant properties, including virucidal efficacy, without the need for the addition of other sanitizing or disinfecting components or separate sanitizing or disinfecting steps. Such a composition would save time and costs, by eliminating the need for additional components or steps. Finally, it is also desirable that such a cleaning composition be stable for an extended shelf life, compatible with other cleaning components and low foaming.
A new alkaline cleaning composition has been developed, which is an improved, stable composition for use alone on hard-to-clean soils. The new composition comprises an alkalinity source, a synergistic combination of surfactants and other components that are phosphate-free and meet detergent regulations for biodegradability, are demonstrated to be stable in the formulation through accelerated stability testing at 50° C. for three months, and have unexpectedly enhanced antimicrobial, including virucidal, efficacy. The composition also contains a stable, UV-analyzable surfactant, which facilitates the detection of the cleaning product at low residue conditions, thus allowing for easy validation of the cleaning process by known techniques. Foam studies conducted on the new formulation, in both graduated cylinders and high-pressure washers at various temperatures and concentrations, showed that they were low foaming. The height of the foam in all cases was similar to currently available alkaline cleaners.
This novel composition offers significant advantages to the prior art in that the product exhibits: superior cleaning of hard-to-clean soils, i.e., effectiveness by itself against both polymeric and oily soils, reduced cleaning time, energy savings, and overall cost reduction; low or no environmental impact, as the composition is phosphate-free and the components of the formulation have proven, established biodegradability; the ability to analyze by HPLC-UV, thus allowing for direct measurement and quantification of the detergent residue and validation of the cleaning process; hospital grade disinfectant properties, including virucidal efficacy; and hard water tolerance.